PROGNOSTIC-SIGNIFICANCE OF DNA CONTENT IN STAGE-I ADENOCARCINOMA OF THE LUNG

Purpose: Up to 30% of lung cancers (Stage I) with the most favorable o utcome recur within 5 years after surgery. This study reviews the patt ern of failure after surgical resection in early lung cancers and dete rmines whether how cytometric DNA variables were prognostic indicators for survival, disease-free survival (DFS), or distant metastasis-free survival (DMFS). Methods and Materials: Pathologic specimens from 45 patients at The University of Texas M. D. Anderson Cancer Center who u nderwent surgical resection and mediastinal nodal dissection for stage I (AJCC) adenocarcinomas of the lung were analyzed by flow cytometry for DNA content. Survival was calculated by the method of Desu and Lee . Chi-square and cross tabulation were used in the analysis. Results: The mean age of the patients was 62 years, and 52.3% were male. All pa tients were clinical Stage I (T1-2 N0), Karnofsky performance status g reater than or equal to 70, and had a weight loss <10 lbs. Median over all survival (OS) and DFS were 50 months and 33 months, respectively. OS, DFS, and DMFS at 1, 3 and 5 years were 73%, 57%, and 35%; 63%, 53% , and 45%; and 67%, 56%, and 48%, respectively. Analysis of all 45 pat ients revealed 86% of patients developing brain metastasis had an abno rmal DNA content greater than or equal to 30%, whereas 4% of patients with brain metastasis had abnormal DNA content <30% (p = 0.01). This c orrelation maintained significance when only pT1/2 lesions were analyz ed. There was a significant statistical correlation between abnormal D NA and 5-year OS, with 74% OS for those with abnormal DNA <30% vs. 42% for greater than or equal to 30% (p = 0.036). The 5-year DFS for pT1/ 2 patients was significantly correlated with abnormal DNA content: 53% for patients with abnormal DNA <30% vs. 17% for patients with abnorma l DNA greater than or equal to 30%, respectively (p = 0.03). Of those with %S fraction (%S) <2, 13% failed locally compared to 41% of those with %S greater than or equal to 2. There was a highly significant cor relation between DNA index (DNAI) and aneuploid %S: 68% of patients wi th a DNAI greater than or equal to 1.7 had greater than or equal to 2. 6 aneuploid %S, whereas only 13% of patients with DNAI greater than or equal to 1.7 had aneuploid %S <2.6. (p < 0.001). Grouping the percent of abnormal DNA and overall %S according to law vs. mixed vs. high va lues correlated with DFS (p = 0.02). Conclusions: This study confirms significant correlation between a high DNA index and a higher frequenc y of brain metastasis, as well as worse OS. Although DNA content varia bles were not predictive of recurrence at other sites, brain metastasi s represents the worst outcome from distant metastasis. Further studie s are needed, as well as prospective trials, for evaluating adjuvant t herapy in patients with adverse DNA variables following complete surgi cal resection for early disease. If high-risk patients could be identi fied after resection, adjuvant therapy (chemotherapy or elective brain irradiation) could be administered. (C) 1998 Elsevier Science Inc.